硫化氢供体对Apo E基因敲除小鼠动脉粥样硬化的调节作用

The effect of hydrogen sulfide donor on the pathogenesis of atherosclerosis in apolipoprotein E knock out mice

目的探讨硫化氢(H2S)供体对Apo E基因敲除小鼠(Apo E-/-)动脉粥样硬化的调节作用。方法6wk龄正常C57BL/6J和Apo E-/-小鼠分为正常对照组、ApoE-/-组和Apo E-/-+硫氢化钠(NaHS)组,每组各8只,普通饮食饲养至16wk龄。分别观察各组小鼠血清中总胆固醇(TCHO)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)含量及主动脉根部斑块面积的变化;用硫电极法测定血清中H2S的含量。结果与对照组相比,Apo E-/-小鼠血清中TCHO[(12.59±3.11vs2.32±0.40)μmol·L-1]和LDL-C[(1.33±0.43vs0.13±0.03)μmol·L-1]水平明显升高,而HDL-C水平[(0.45±0.13vs1.49±0.21)μmol·L-1]明显降低,血清中H2S的含量[(44.64±4.52)μmol·L-1]较对照组[(57.69±7.03)μmol·L-1]明显下降,主动脉根部明显出现斑块[(139316.6±30362.93vs0)μm2];给予NaHS后,Apo E-/-小鼠血清中TCHO、LDL-C和HDL-C水平无明显变化,而血清中H2S的含量明显升高[(52.21±7.24vs44.64±4.52)μmol·L-1],主动脉根部动脉粥样硬化斑块明显缩小[(85927.84±1922.73vs139316.6±30362.93)μm2]。结论新型气体信号分子H2S可以延缓动脉粥样硬化的进程,缩小动脉粥样硬化斑块形成。

Aim To explore the effect of hydrogen sulfide （H2S） donor on the pathogenesis of atherosclerosis in apolipoprotein E knock out mice （Apo E^-/- Methods 6-week old C57BL/6J and Apo E^ -/- mice were divided into normal group, Apo E^ -/- group and Apo E^ -/- ＋ sodium hydrosulfide （NariS） group, with 8 mice in each group. They were fed chow diet until 16- week old. The serum levels of total cholesterol, low density lipoprotein and high density lipoprotein were determined and the changes of atheroselerosis plaque size were observed. Sulfide electrode-based method was used to measure the serum level of H2 S. Results The serum levels of total cholesterol[ （ 12.59 ± 3.11 vs 2. 32 ±0. 40） μmol · L^-1 ] and low density lipoprotein [（1.33±0.43 vs 0. 13 ±0.03） μmol· L^-1] in Apo E^ -/- mice were significantly higher than those in normal group, while the serum levels of high density lipoprotein [ （ 0. 45 ± 0. 13 vs 1.49± 0. 21 ） μmol · L^- 1]and H2S in Apo E^-/- mice[ （44.64 ±4. 52 vs 57.69 ± 7.03 ） μmol · L^-1] were significantly lower than those in normal group. Meanwhile, the atherosclerosis plaque[ （139316. 6 ± 30362.93 vs 0） μm^2] was obvious in Apo E^-/- mice. After NariS was administrated, there were no obvious changes in the serum levels of total cholesterol, low density lipoprotein and high density lipoprotein in Apo E^-/- mice, while the serum level of H2S [ （ 52. 21 ±7.24 vs 44. 64 ± 4. 52 ） μmol · L^-1 ] increased significantly and the size of atherosclerosis plaque[ （85927.84 ± 1922.73 vs 139316. 6 ± 30362.93 ） μm^2 ] diminished significantly. Conclusions H2 S postponed the proceeding of atherosclerosis and diminished the size of atherosclerosis plaque.